“Survival is promising, particularly in patients with CR, PR, or SD,” added Adams.

These data follow the positive activity with pembrolizumab in TNBC demonstrated in the phase Ib KEYNOTE-012 trial. In the study, 32 patients with PD-L1–positive heavily pretreated TNBC received intravenous pembrolizumab at 10 mg/kg every 2 weeks. The ORR was 18.5%, which included 1 CR (3.7%) and 4 partial PRs (14.8%).2 Additionally, seven patients had SD (25.9%), 1 of which persisted for ≥24 months.

Cohort A of KEYNOTE-086 (NCT02447003) included 170 patients with metastatic TNBC who had received at least 1 prior line of chemotherapy for metastatic disease. The median age was 54 years, 82.4% of patients were postmenopausal, 47.1% of patients had an ECOG performance status of 1, and 62% had PD-L1–positive tumors. Elevated LDH was reported for 51% of patients, 74% had visceral metastases, and 44% had received 3 or more prior lines of therapy.

Pembrolizumab was administered at 200 mg IV every 3 weeks until disease progression, intolerable toxicity, or a maximum of 2 years. Tumors were evaluated through imaging every 9 weeks for the first year, and then every 12 weeks thereafter. Patients with progressive disease who remained clinically stable could continue pembrolizumab until progressive disease was confirmed on the next evaluation.

At the data cutoff of November 10, 2016, the median follow-up was 10.9 months (range, 7.7-15.5) and 9 (5.3%) patients remained on pembrolizumab. Responses occurred in 8 patients, including 1 CR, and 7 PRs. Twenty-seven percent of patients had a decrease in target lesion size from baseline. Progressive disease was reported for 60.6 % (n = 103) of patients.

PD-L1 status was not associated with response, as the ORR was 4.8% in PD-L1–positive patients and 4.7% in PD-L1–negative patients.

The median time to response was 3.0 months (range, 1.9-8.1). The disease control rate (CR + PR + SD ≥24 weeks) was 7.6%. The median PFS was 2 months (95% CI, 1.9-2.0) and the median OS was 8.9 months (95% CI, 7.2-11.2). The 6-month PFS and OS rates were 12% and 69%, respectively. There was not a significant difference in PFS or OS in the PD-L1–positive versus –negative cohorts.

In patients with poor prognostic factors, the ORR was lower. The ORR was 2% in patients with elevated LDH compared with 7% in patients with normal or low LDH. In patients with visceral metastases, the ORR was 2% compared with 11% in patients with no visceral metastases. No patients with liver metastases had a response.

The median time on therapy was 56.5 days and the median number of doses was 3. At the time of the analysis, 161 patients (94.7%) had discontinued treatment. The majority of patients discontinued due to disease progression; 7 patients (4.1%) discontinued due to adverse events (AEs).

All-grade treatment-related adverse events (TRAEs) occurred in 60% of patients, with 12.4% of patients experiencing grade 3/4 TRAEs. The most common all-grade AEs were fatigue (20.6%) and nausea (10.6%).

All-grade immune-mediated AEs occurred in 18.8% of patients, only 1.2% of which were grade 3/4, and none of which led to death. The most common all-grade immune-mediated AEs were hypothyroidism (11.2%), hyperthyroidism (4.7%), and pneumonitis (3.5%). There were no deaths related to AEs.

Adams also shared some initial results from cohort B of KEYNOTE-086, which included data for 52 women with previously untreated PD-L1 positive metastatic TNBC. The ORR in this cohort was 23.1%. Additionally, 50% of the patients had a decrease in targeted lesion size.

In her concluding remarks, Adams said, “The results of ongoing trials of pembrolizumab as monotherapy and pembrolizumab-based combination therapies will further define the role of PD-1 blockade in TNBC.”